A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand.

Abstract

Abstract. The efficacy-safety and pharmacokinetics of the six-dose regimen of artemether-lumefantrine (Coartem/ Riamet; Novartis Pharma AG, Basel, Switzerland) were assessed in a randomized trial in 219 patients (Ն 12 years old) with acute, uncomplicated Plasmodium falciparum malaria in Thailand. One hundred and sixty-four patients received artemether-lumefantrine and 55 received the standard treatment combination of mefloquine-artesunate. Both drugs induced rapid clearance of parasites and malaria symptoms. The 28-day cure rates were 95.5% (90% confidence interval [CI] ϭ 91.7, 97.9%) for artemether-lumefantrine and 100% (90% CI ϭ 94.5, 100%) for mefloquine-artesunate. This high-dose regimen of artemether-lumefantrine was very well tolerated, with very good compliance. The most frequent adverse events were headache, dizziness, nausea, abdominal pain, dyspepsia, vomiting, and skin rash. Overall, only 2% of patients in both groups showed QTc prolongations but without any cardiac complication, and no differences were seen between patients with and without measurable baseline plasma levels of quinine or mefloquine. Plasma levels of artemether, dihydroartemisinin, and lumefantrine were consistent with historical data for the same dose regimen, and were higher, particularly for lumefantrine, than those previously observed with the four-dose regimen, explaining the greater efficacy of the six-dose regimen in a drug-resistant setting. These results confirm the excellent safety and efficacy of the six-dose regimen of artemether-lumefantrine in the treatment of multidrug-resistant P. falciparum malaria.

Efficacy of six-dose regimen of artemether-lumefantrine for the treatment of uncomplicatedfalciparummalaria, three years after its introduction into Ethiopia

“…This is comparable with the previous study that showed a high treatment success rate (99.1 %) in the country (Jima et al, 2005b). The finding of this study is also in agreement with other studies in children and adults elsewhere using ACTs (Van Vugt et al, 1999, 2000Lefevre et al, 2001;Flade et al, 2005;Jima et al, 2005b;Piola et al, 2005;Piola et al, 2005;Guthmann et al, 2006;Van den Broek et al, 2006;Adama et al, 2007). In a study conducted in Senegal, the efficacy of AL was found to be 100 % when given as six doses, while it was found to be reduced by 3.6 % when given as four doses (Faye et al, 2007).…”

“…The present result also indicated the importance of maintaining the sixdose regimen for the treatment of uncomplicated falciparum malaria with regularly monitoring for its effectiveness especially in areas where multi-drug resistance falciparum malaria is common (Hastings et al, 2007). In this study, treatment with AL was also found to induce rapid clearance of malaria symptoms which is in agreement with previously conducted study in Ethiopia and clinical studies conducted elsewhere using ACTs (Bakshi et al, 2000;Lefevre et al, 2001;Jima et al, 2005b;Mulenga et al, 2006;Menard et al, 2008). In addition to its rapid parasitological and malaria symptoms clearance, AL showed high gametocyte reduction during the follow-up.…”

“…In a study conducted in Senegal, the efficacy of AL was found to be 100 % when given as six doses, while it was found to be reduced by 3.6 % when given as four doses (Faye et al, 2007). Study by Lefevre et al (2001) showed a high efficacy and safety of six-dose of AL when administrated as four tablets twice daily for three consecutive days. Moreover, a pooled analysis of individual patient data confirmed higher efficacy of six-dose regimen of AL compared to four-dose regimen in children (Makanga et al, 2006).…”

“…Series evidences have shown high efficacy of ACTs against P. falciparum even in multidrug-resistant strains of the parasite (Lefevre et al, 2001;Makanga et al, 2006;Adama et al, 2007;Menard et al, 2008;Kaddouri et al, 2008). Nevertheless, substantial re-assessment of the efficacy of this combination therapy against P. falciparum is crucial to monitor possible emergence of resistance and ensuring a continued coverage of effective treatment.…”

High efficacy of two artemisinin‐based combinations (artemether–lumefantrine and artesunate plus amodiaquine) for acute uncomplicated malaria in Ibadan, Nigeria

“…Coartemether (CoartemÒ, Novatis Pharma), a fixed dose combination of artemether and lumefantrine, combines the rapid but shortlived schizonticidal effect of artemether with the slower but more prolonged antimalarial effect of lumefantrine, a highly lipophilic aryl amino alcohol (Lefèvre et al 2001). When administered alone as a short treatment course over 2-3 days, lumefantrine gives a high cure rate but parasite and fever clearance time is slower than with artemether.…”